title: PTP1B contributes to calreticulin-induced metastatic phenotypes in esophageal squamous cell carcinoma.
abstract: Calreticulin (CRT) is a Ca(2+)-binding chaperone protein that alters cellular Ca(2+)-homeostasis in the endoplasmic reticulum (ER). Previously it was shown that CRT was overexpressed in esophageal squamous cell carcinoma (ESCC), and elevated CRT expression promoted the migration and invasion of ESCC cells. In the present study, the mechanisms underlying the role of CRT in esophageal carcinoma progression were investigated. Critically, depletion of CRT or protein-tyrosine phosphatase 1B (PTP1B) reduced ESCC cell migration and metastasis to the lung, whereas restoration of PTP1B protein levels rescued cell migration in CRT-silenced cells. Knockdown of CRT decreased PTP1B protein expression by reducing phosphorylation at the Y694 site of STAT5A, whereas knockdown of PTP1B reduced ERK1/2 phosphorylation at T204. Immunohistochemical analysis of CRT and PTP1B expression in ESCC patient tissues was strongly correlated. Importantly, PTP1B expression was associated with poor survival in patients with CRT overexpression. Overall, these data indicate a novel signaling pathway connecting CRT, STAT5A, PTP1B, and ERK1/2 in the regulation of ESCC cell migration.
  
  
  CONCLUSIONS
  These findings suggest that PTP1B is a downstream effector of CRT signaling, promotes tumor progression, and can potentially be used as a new drug target for ESCC.
authors.affiliation: State Key Laboratory of Molecular Oncology, Cancer Institute (Hospital), PUMC/CAMS, 17 Panjiayuan Nanli, Chaoyang District, Beijing 100021, China. wangmr2015@cicams.ac.cn.
authors.forename: Xiao-Min
authors.initials: XM
authors.lastname: Wang
authors.forename: Li
authors.initials: L
authors.lastname: Shang
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jia-Jie
authors.initials: JJ
authors.lastname: Hao
authors.forename: Feng
authors.initials: F
authors.lastname: Shi
authors.forename: Wei
authors.initials: W
authors.lastname: Luo
authors.forename: Tong-Tong
authors.initials: TT
authors.lastname: Zhang
authors.forename: Bo-Shi
authors.initials: BS
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Liu
authors.forename: Qi-Min
authors.initials: QM
authors.lastname: Zhan
authors.forename: Ming-Rong
authors.initials: MR
authors.lastname: Wang
mesh_terms: D000818:Animals; D037282:Calreticulin / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D018450:Disease Progression; D004938:Esophageal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D051379:Mice; D016513:Mice, SCID; D058990:Molecular Targeted Therapy; D010641:Phenotype; D010766:Phosphorylation; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
chemical_list: D037282:Calreticulin; D012333:RNA, Messenger; D050799:STAT5 Transcription Factor; C494092:STAT5A protein, human; D025521:Tumor Suppressor Proteins; C516607:PTPN1 protein, human; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1